A major problem encountered in genomic and proteomic studies arises from the heterogeneous nature of different tissue. Analysis of a pure cell population is essential for correlating relevant molecular signatures in diseased and disease-free cells. During the last 30 years this challenge has led to the development of different technologies able to isolate cells of interest. Laser capture microdissection (LCM) is the last available technology using the precision of a laser beam to isolate single cells from complex tissue. In this chapter we will review the different technologies available and some applications.