Our Method of the Year 2014 goes to light-sheet fluorescence microscopy. This series of papers discusses how this technology, in combination with increasingly sophisticated cameras and powerful computing, is dramatically changing and enabling the imaging of living biological samples from developing embryos to functioning brains. We also highlight methods worth watching in the upcoming years.

Nature Methods is ten years old. In this anniversary issue, we highlight our choice of the ten areas of methods development with the most impact on biological research over the past decade, and feature commentaries on a subset of these methods. Visit Methagora to browse Nature Methods papers in these areas.

Synthetic biology spans many disciplines and has many different goals but all rely on well-characterized basic tools. In this Focus experts discuss the current status of essential methods, going from DNA synthesis to genetic circuit design to whole genome assembly and how these tools can be deployed for applications from medical research to addressing the origin of life.

Since its inception almost 15 years ago, synthetic biology has evolved into a vibrant and productive field, owing in large part to the use of model microorganisms for the design, creation and implementation of both simple and more sophisticated biological systems. This Focus issue of Nature Reviews Microbiologypresents a set of specially commissioned articles that together chart the technological and cultural developments of the field, provide a framework for the use of emerging synthetic devices for microbial engineering, discuss the use of alternative microorganisms for industrial-scale applications and describe the first successful 'real-world' application that has been achieved. The Focus issue is accompanied by a joint Web Special withNature MethodsandNature.

The 2014 Nobel Prize in Chemistry was awarded for the development of superresolution fluorescence microscopy, which enables the imaging of fine biological structures previously thought to be unresolvable using light. This collection of news pieces and articles by the Nobel laureates and their collaborators celebrates this achievement.

Nature Methods' choice for Method of the Year 2013 is single-cell sequencing. A collection of articles present the unique considerations related to sequencing single cells and highlight recent applications in biology and medicine. The Methods to Watch feature provides a look at possible future Methods of the Year.

We are entering a new era in the neurosciences, in which development of technology will be in the spotlight. In this Focus, experts outline the different technologies needed to obtain anatomical and functional brain maps across species, and discuss the importance of assembling these maps and what will be needed beyond them, to understand the functioning of the brain.

The use of a planar sheet of light for illumination in fluorescence microscopy allows researchers to image sample Vol.s faster than possible with other current methods, while limiting light dosage. This collection of articles provides a brief overview of this exciting methodology and the biological research applications that it makes possible.

A selection of Technology Features published in Nature and Nature Methods over the past year highlights topics in microscopy, antibodies, cell heterogeneity, epigenetics, genome editing, post-translational modifications, PCR, stem cell–niche engineering, cell culture media, in vivo imaging, synthetic biology and genome analysis workflows and tools.

Nature Methods' choice for Method of the Year 2012 is targeted proteomics. A collection of articles showcases how mass spectrometry technology is being developed and applied for targeted protein analysis in both basic and translational research.

Explosive growth in the size and complexity of microscopy-based imaging data and the need to extract more quantitative data from it increasingly requires sophisticated image acquisition and analysis methods and software tools. A collection of articles discusses the role of bioimage informatics in microscopy, specific tools that are available, and the challenges and opportunities in the field.

Nature Methods' choice for Method of the Year 2011 is genome editing with engineered nucleases. This collection of articles—and the related video—highlights how the ability to use engineered nucleases to make precise, tailored and specific changes to coding and noncoding sequences of the genome, in cells and in organisms of many species, could revolutionize the study of gene function.