Knowledge sharing has become an important issue in the eHealth field for improving the quality of healthcare service. However, since eHealth subject is a multidisciplinary and cross-organizational area, knowledge sharing is a serious challenge when it comes to developing eHealth systems. Thus, this thesis studies the heterogeneous knowledge sharing in eHealth and proposes a knowledge sharing ontology. The study consists of three main parts: modeling, validation and application. In the modeling part, knowledge sharing in eHealth is studied from two main aspects: the first aspect is the heterogeneous knowledge of different healthcare actors, and the second aspect is the interactivities among various healthcare actors. In this part, the contribution is to propose an Activity Theory based Ontology (ATO) model to highlight and represent these two aspects of eHealth knowledge sharing, which is helpful for designing efficient eHealth systems. In the validation part, a questionnaire based survey is conducted to practically validate the feasibility of the proposed ATO model. The survey results are analyzed to explore the effectiveness of the proposed model for designing efficient knowledge sharing in eHealth. Further, a web based software prototype is constructed to validate the applicability of the ATO model for practical eHealth systems. In this part, the contribution is to explore and show how the proposed ATO model can be validated. In the application part, the importance and usefulness of applying the proposed ATO model to solve two real problems are addressed. These two problems are healthcare decision making and appointment scheduling. There is a similar basic challenge in both these problems: a healthcare provider (e.g., a doctor) needs to provide optimal healthcare service (e.g., suitable medicine or fast treatment) to a healthcare receiver (e.g., a patient). Here, the optimization of the healthcare service needs to be achieved in accordance with eHealth knowledge which is distributed in the system and needs to be shared, such as the doctor’s competence, the patient’s health status, and priority control on patients’ diseases. In this part, the contribution is to propose a smart system called eHealth Appointment Scheduling System (eHASS) based on ATO model. This research work has been presented in eight conference and journal papers, which, along with an introductory chapter, are included in this compilation thesis.