Spreading of cancer cells to effusions is a manifestation of advanced disease, for which the chances of achieving cure using conventional treatment are low. This emphasizes both the importance of improving early detection and the need for developing targeted therapy modes. Such approaches should be based on characterization of the antiapoptotic, survival and drug resistance mechanisms of the metastatic cells in addition to analysis of the primary tumor. This review presents current knowledge regarding the expression and clinical role of cell survival and apoptosis-related molecules in nonhematological cancers in effusions. Differences in the anatomic site-related expression and clinical role of these proteins are additionally discussed. The data presented highlight the complexity of the multiple molecular pathways that mediate tumor cell survival within the serosal cavities.