Jehovah’s Witnesses are primarily known to physicians for their refusal of blood transfusions. Conflict arises at times with the medical staff concerning how best to manage their care. This article will begin with a brief description of the beliefs of Jehovah’s Witnesses and will then recommend specific clinical strategies highlighting newer potential therapies according to the principles of bloodless medicine. The scenarios of bleeding and acute and chronic anemia will be discussed in detail for the care of these patients refusing red blood cell transfusions. An update in the use of blood substitutes will be mentioned as well as the surgical advances used today that can minimize blood loss for all patients. The experience of organ transplantation in Jehovah’s Witnesses will be detailed. Further resources for physicians with questions in the care of these patients will be listed. Stressed throughout the article will be the need for a team approach and good communication between physicians to successfully care for their patients who are Jehovah’s Witnesses.