Approximately 80% of adult patients with immune thrombocytopenia (ITP) fail or become dependent on corticosteroids and require second-line therapy. Several new and effective therapies have been introduced during the last decade and our understanding of disease burden and its effect on quality of life has expanded. It is now recommended that splenectomy, the standard second-line therapy for decades, be delayed for at least 12-24 months allowing more patients to achieve remission on medical therapies before considering surgery. It is highly recommended to use medical therapies with abundant clinical trial evidence such as thrombopoietin receptor agonists (TPO-RA), rituximab or fostamatinib. Unfortunately, there are no reliable biomarkers that help in treatment selection. These therapeutic medical options have variable efficacy, safety profiles, mechanism of action and mode of administration. This allows and mandates an individualized approach to treatment, where patient involvement, preferences and values have become central to the process of choosing the appropriate therapy. Both TPO-RA and fostamatinib are maintenance therapies whereas rituximab is given for a limited number of doses. While response is usually maintained while on therapy with TPO-RA or fostamatinib, half of rituximab responders will lose response 1 to 2 years after administration and require retreatment or other therapy.