Caspase-3 plays a vital role in intrinsic and extrinsic pathways of programed cell death and in cell proliferation. Its detection is an important tool for early detection of some cancers and apoptosis-related diseases, and for monitoring the efficacy of pharmaceuticals and of chemo- and radiotherapy of cancers. This review (with 72 references) summarizes nanomaterial based methods for signal amplification in optical methods for the determination of caspase-3 activity. Following an introduction into the field, a first large section covers optical assays, with subsections on luminescent and chemiluminescence, fluorometric (including FRET based), and colorimetric assays. Further section summarize methods for bioimaging of caspase-3. A concluding section covers current challenges and future perspectives.