Whole slide imaging (WSI) is a versatile technology with many applications in teaching, research, quality assurance, and clinical diagnostics. As a “store and forward” digital imaging technology, WSI is naturally suited to distribution over high-speed communication networks, which enables long-distance viewing of whole slide images originating at remote locations. For this reason, WSI is being applied to the practice of telepathology—literally “the study of disease at a distance.” Changes in the practice and business of medicine have been driving adoption of telepathology in recent years. Anyone looking to implement WSI telepathology needs to recognize and understand key aspects covered in this chapter. Technical considerations are key to creating usable telepathology networks. This includes understanding how network performance influences the function of WSI telepathology systems and how optimal deployment of hardware and software can help you meet your business needs and technical requirements. It is also important to recognize the advantages and disadvantages of WSI when compared to other telepathology modalities such as static image telepathology, dynamic telepathology, and robotic telepathology. In addition to technical considerations, practicing telepathology with WSI also raises regulatory and legal issues. These issues include specific features of in vitro device regulation, medical licensure, privileging and credentialing, and compliance with the Center for Medicare and Medicaid Services (CMS) and Clinical Laboratory Improvement Amendments (CLIA) regulations. Finally, laboratory accreditation requirements and issues with reimbursement for telepathology service are also discussed.