Single cell analysis in a microfluidic device proceeds through a certain number of steps. The two first steps of the protocol are the manipulation of individual cells in the microfluidic device and their positioning in precise locations and subsequently the process to rupture the cell membrane to retrieve the cellular content. In this chapter, we will focus on these two first steps of cell trapping and single cell lysis, and review different approaches and techniques found in the literature for these two steps to achieve these in a microfluidic format. We will also discuss the advantages and limitations of the different techniques of manipulation, trapping and lysis.