Hand-foot syndrome (HFS) and nail changes are frequent adverse events of anticancer therapies. To provide areview of current evidence in HFS and nail disorders associated with medical tumor treatment. Basis is the current German S3guideline "Supportive therapy in oncologic patients" and literature on this topic published since the guideline was finalized. Two variants of HFS are distinguished: achemotherapy-associated and akinase-inhibitor-associated variant. In the first form, painful erythema, blisters and ulceration can occur, also in other areas with ahigh number of sweat glands such as axillary and inguinal regions. Thus, the secretion of toxic substances through sweat glands is aproposed pathogenetic mechanism. For the second form, which results in callus-like painful thickening of the horny layer on areas of mechanic pressure, avascular mechanism is proposed. For prophylaxis of HFS, avoidance of mechanical stress, regular cleaning of predisposed areas, and also urea- and diclofenac-containing ointments are recommended; in case of infusions (taxanes, doxorubicine), cooling of hands and feet during infusion is recommended. In case of manifest HFS, dose reduction or prolongation of intervals of the associated treatment are recommended. Nail changes often develop under therapy with chemotherapeutic agents but also under treatment with agents such as checkpoint inhibitors or under targeted therapy. Different components of the nail unit may be involved such as the nail matrix, nail bed, nail plate, hyponychium, lunula and proximal and lateral nail folds. This work gives insight into the pathophysiology of HFS and nail disorders that develop under systemic oncologic treatments and gives recommendations for prophylaxis and treatment.