Itching (pruritus) and sweating (perspiration, diaphoresis) are physiological functions of the skin that normally serve human existence well. Itching is the sensory input arising from the skin and mucous membranes that alerts man to potentially harmful insults from physical, chemical, and biological sources. The reflex of scratching is closely linked to the perception of itch, and in most situations functions effectively as an aversive motor response to relieve the sensation and protect the skin. Similarly, sweating is a well-developed and finely coordinated sudomotor response designed to regulate body temperature and prevent hyperthermia. However, both pruritus and sweating have the potential to function aberrantly and develop into pathological conditions that create significant suffering and morbidity. This chapter provides a practical overview of the normal function and pathophysiology of pruritus and sweating, and offer a variety of therapeutic options and general comforting measures for patients experiencing these maladies.