Disclosed are methods for classifying a patient with cancer as a candidate for therapy with a Bcl-2 family inhibitor comprising determining the level of at least one biomarker in a sample and comparing the biomarker level to a threshold level. Also described are methods for identifying classes of patients having a refractory cancer for second-line therapy comprising a Bcl-2 family inhibitor, where the method comprises determining the level of at least one biomarker in a sample and comparing the biomarker level to a threshold level.