The functional sequence space for cell penetrating peptides (CPPs) is vast. Recent data from computational, synthetic, and biological systems show that the mechanisms by which they bypass membranes are similarly diverse.The CPP mechanism is mutable; it is not determined by the peptide sequence only. Many other experimental and biological factors are important, including local peptide concentration, local lipid composition, and the properties of the cargo.The position of a CPP within the mechanistic taxonomy, under one set of conditions, can be described by the degree to which it is taken up by endocytosis, and the degree to which it can disrupt membranes.Transformation from a peptide-centric approach to a mechanistic and cargo-centric approach may enable the CPP field to fulfill its long-held promise.