The condition of separation-related problems (SRPs) is common in companion dogs and clinicians should be comfortable diagnosing it. There are numerous diagnoses related to physical disease that have clinical signs similar to SRP, that exacerbate SRP, or may cause regression in treatment of SRP. Common examples include conditions affecting the following systems: musculoskeletal, neurologic, gastrointestinal, and dermatologic. Therefore, it is important for clinicians to rule out causes of physical disease and address them accordingly. The signalment of the patient, medications they are receiving, and other behavioral comorbidities should also be considered.