Microvascular occlusions caused by sickle cell disease (SCD) can affect all ocular and orbital structures. Sickle cell retinopathy (SCR) is the most common ophthalmic manifestation of SCD. Fortunately, most individuals with SCR are visually asymptomatic. Vision loss in SCD most commonly occurs as a consequence of proliferative sickle cell retinopathy (PSR), in which pathologic retinal neovascularization occurs. To prevent significant vision loss and blindness, which can occur from complications of PSR, regular retinopathy surveillance screening examinations and consistent follow-up with a retina specialist are recommended. Scatter laser photocoagulation is the current gold-standard treatment to prevent vision threatening progression of PSR. Patients with sickle cell disease should have regular checkups with their dental care provider. Patients should be educated on the importance of proper dental care, a healthy diet, and the need for early intervention if they suspect any dental problems or are having dental pain. If any dental procedures that involve surgery or sedation are planned, it is critical to consult with the hematologist before the procedure is started. Prophylactic antibiotics may have to be prescribed before invasive dental procedures, such as extractions or periodontal surgery but is best determined by discussions between the dental care provider and the hematologist. Osteonecrosis is a highly prevalent skeletal complication of sickle cell disease that affects all genotypes. Risk factors for osteonecrosis include older age, HbSS genotype with concomitant alpha-thalassemia trait, frequent vaso-occlusive episodes, history of acute chest syndrome, elevated body mass index, and low white blood cell counts. Osteonecrosis causes progressive joint damage and associates with chronic pain, frequent acute care visits, and overall poor health-related quality of life. Current consensus guidelines recommend analgesics, physical therapy, and early consideration of joint arthroplasty in sickle cell-related osteonecrosis, although surgery may be deferred until late adolescence after growth plates have fused.