The utilization of macromolecules in therapy of cancer and other diseases is becoming increasingly relevant to successful tumor therapy. Recent advances in molecular biology and biotechnology have made it possible to improve targeting and design of cytotoxic agents, DNA complexes and other macromolecules for clinical applications. To achieve the expected biological effect of these macromolecules, in many cases, internalisation to the cell cytosol is crucial. Macromolecules are frequently prohibited from penetrating cell membranes, are instead, endocytosed and without any active intervention become degraded by hydrolytic enzymes in the lysosomes. Thus, at an intracellular level, the most fundamental obstruction for cytosolic localization of therapeutic macromolecules is the membrane‐barrier of the endocytic vesicles. Photochemical internalisation (PCI) is a novel technology for release of endocytosed macromolecules into the cytosol. PCI has been shown to potentiate the biological activity of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane.