Immune thrombocytopenia is one of the most common causes of thrombocytopenia seen in classical hematology practice, with a prevalence of approximately 2.6–9.5 per 100,000 individuals. Over the last decade, numerous new treatments for immune thrombocytopenia (ITP) have emerged, which have significantly improved the management of this disorder. However, largely due to the paucity of randomized trials in ITP and the heterogeneity of this disorder, the optimal sequencing of new and pre-existing therapies in ITP remains uncertain. In addition, there remains no “gold standard” diagnostic test for ITP, and the many causes of thrombocytopenia encountered in clinical practice may render the appropriate diagnosis of ITP difficult. Finally, even with an increasing number of available therapeutic options, occasional patients with refractory ITP are encountered, and their management may be challenging. Similarly, the limited options available for treatment of ITP in pregnancy continue to present obstacles. In this review, we will provide a brief introduction to ITP and present five cases that illustrate diagnostic and management dilemmas in ITP; approaches to these cases will provide insight into management of challenging cases of ITP in practice.