Examples of operator algebras with involution include the operator * -algebras occurring in noncommutative differential geometry studied recently by Mesland, Kaad, Lesch, and others, several classical function algebras, triangular matrix algebras, (complexifications) of real operator algebras, and an operator algebraic version of the complex symmetric operators studied by Garcia, Putinar, Wogen, Zhu, and others. We investigate the general theory of involutive operator algebras, and give many applications, such as a characterization of the symmetric operator algebras introduced in the early days of operator space theory.