The foot is the target organ of a variety of internal diseases. Of upmost importance is the diabetic foot syndrome (DFS). Its complex pathophysiology is driven by the diabetic neuropathy, a vastly worsening effect is contributed by infection and ischemia. Seemingly localised lesions have the potential for phlegmone and septicaemia if not diagnosed and drained early. The acral lesions of peripheral artery occlusive disease (PAOD) have unique features as well. However, their life-threatening potential is lower than that of DFS even if the limb is critical. Notably, isolated foot lesions with a mere venous cause may arise from insufficient perforator veins; the accompanying areas of haemosiderosis will lead the diagnostic path. Cholesterol embolization (blue toe syndrome, trash foot) elicits a unique clinical picture and will become more frequent with increasing numbers of catheter-based procedures. Finally, descriptions are given of podagra and of foot mycosis as disease entities not linked to perfusion. The present review focuses on the depiction of disease and its diagnosis, leaving therapeutic considerations untouched.