Recent developments in micro and nano technologies allow for the controlled manipulation of individual molecules by exerting and detecting forces in the piconewton range. The possibility to detect such tiny forces together withe the ability of measuring extensions with nanometer resolution allows to characterize the thermodynamics and kinetics of individual molecules (e.g. nucleic acids and proteins) within 1kcal/mol energy resolution.

In this talk I will review some recent theoretical developments and present new experimental results on single molecule manipulation of nucleic acids aiming to explore the nonequilibrium behavior of small systems. I will discuss fluctuation theorems and show how it is possible to design specific DNA sequences with complex free energy landscapes to investigate the kinetics of folding.