Cell death research during the last decades has revealed many molecular signaling cascades, often leading
to distinct cell death modalities followed by immune responses. For historical reasons, the prototypic and
best characterized cell death modes are apoptosis and necrosis (dubbed necroptosis, to indicate that it is
regulated). There is mounting evidence for the interplay between cell death modalities and their redundant
action when one of them is interfered with. This increase in cell death research points to the need for
characterizing cell death pathways by different approaches at the biochemical, cellular and if possible,
physiological level. In this review we present a selection of techniques to detect cell death and to distinguish
necrosis from apoptosis. The distinction should be based on pharmacologic and transgenic
approaches in combination with several biochemical and morphological criteria. A particular problem
in defining necrosis is that in the absence of phagocytosis, apoptotic cells become secondary necrotic
and develop morphologic and biochemical features of primary necrosis.