Knowtator is a general-purpose text annotation tool that is integrated with the Protégé knowledge representation system. Knowtator facilitates the manual creation of training and evaluation corpora for a variety of biomedical language processing tasks. Building on the strengths of the widely used Protégé knowledge representation system, we have developed Knowtator as a Protégé plugin that leverages Protégé’s knowledge representation capabilities to specify annotation schemas. Knowtator’s unique advantage over other annotation tools is the ease with which complex annotation schemas (e.g. schemas which have constrained relationships between entity types) can be defined and incorporated into use. Additionally, because annotation schemas are defined using a Protégé ontology, it is straightforward to incorporate domain knowledge into an annotation schema for semantic annotation.