The ultimate aim of cancer therapeutics is to eradicate tumor cells. Upon lethal exposure to chemotherapeutic agents, cells undergo apoptosis-an active, energy-requiring, programmed cell death. Apoptosis follows a well-orchestrated activation of cysteine proteases, known as caspases. In normal conditions, all the caspases exist as inactive procaspases; they require proteolytic cleavage for activation. A variety of methods are currently used to detect procaspases and caspases and their activity. Immunodetection and fluorescent substrates are widely accepted methods that are utilized for this purpose. These methods are described in detail in this chapter.