Chronic lymphocytic leukemia (CLL) is a highly heterogeneous hematologic malignancy and characterized by dysregulation of cell death pathways. Apoptosis and necroptosis are the two major cell death processes, and substantial evidence showed up-regulation of several pro-survival factors in CLL cells. Autophagy, as a dual player in mediating cell death and survival, is largely regarded to be an alternative target in the treatment of CLL. Numerous novel drugs have been developed and are being investigated in clinical trials. It is necessary to depict the impaired cell death pathways in CLL and the pro-survival factors targeted by noncytotoxic drugs directly or indirectly. Here we summarize three dysregulated cell death mechanisms in CLL, and present the current knowledge of drugs that orchestrate cell death via targeting pro-survival factors and the clinical effects as well.