Increasing investigative efforts have been focused on the application of in vitro clonogenic assays for human tumors. Several semisolid matrices have been used for purposes of immobilizing the clonogenic cells, and a variety of growth factors and environmental conditions have been studied to enhance tumor colony growth. Although there remain some technical problems with these assays, the methodology has proven to have broad applicability to preclinical and clinical studies of human cancer. This report reviews some features and areas of application of this assay methodology. The ability to combine studies of drug effect with cytogenetic studies on clonogenic cells suggests that such assays may prove useful for evaluation of the emergence of drug resistance by primary and metastatic cancers.