Background: Lithium treatment has been associated with hyperparathyroidism (HPT). However, there are conflicting data regarding the rate of single- (SGD) versus multiple-gland disease (MGD) as well as the optimum surgical approach in these cases. Methods: Published data were identified through systematic electronic literature searches. Studies that fulfilled the preset inclusion criteria were analyzed (n = 12). Results: These studies documented 210 lithium-associated HPT (LAH) cases. Of these, 103 (49%) were due to SGD and 107 (51%) due to MGD. The unadjusted odds ratio of having multiple LAH compared to sporadic HPT was 3.44 (95% confidence interval 2.5907-4.5633; p < 0.0001). The sensitivity of preoperative sestamibi and sonography for SGD was 66-100 and 75-82%, respectively. The sensitivity for MGD was 9-67% for both. Intraoperative parathyroid hormone monitoring was utilized in 6 studies. Three studies recommended minimally invasive parathyroidectomy (MIP), while the other 3 recommended bilateral exploration. Conclusion: LAH is a relatively frequent condition among patients on lithium, and calcium monitoring should be performed initially and longitudinally. Almost half of the LAH cases are due to SGD. MIP should be the optimum surgical approach.