This article focuses on the current state of knowledge concerning the characterization and classification of palmoplantar keratoderma and associated syndromes. In addition, therapeutic options are discussed. Exact diagnosis enables dermatologists to give patients accurate genetic counseling and may help to detect underlying defects or proneness to cancer. Furthermore, precise classification of this disease facilitates the use of the most efficient therapeutic modalities. Important criteria for the classification of palmoplantar keratoderma are the mode of transmission, age at onset, and distribution of the keratoderma. The disorder may be diffuse or focal; it may be restricted to the palms and soles or also involve the dorsal aspects of the hands and feet. Psoriatic-like lesions in other parts of the body may occur in certain variants. The association of other signs and symptoms may provide diagnostic clues. Ultrastructural investigation will show diagnostic features in some types of palmoplantar keratoderma, and biochemical analysis may be helpful in the classification of keratoderma. In the future, the most accurate diagnosis will be the identification of the genetic defect and its chromosomal localization.