In the last decade, rituximab and thrombopoietin-receptor agonists (TPO-ra) have been introduced into the traditional armamentarium of Immune Thrombocytopenia (ITP), consisting in corticosteroids as initial treatment and splenectomy in those not responding or relapsing. A variety of immunosuppressive treatments were reserved for patients not responsive to splenectomy. These advancements have been incorporated in two international current guidelines: the first, produced by an international group of expert clinicians (International Consensus Report, ICR); the second, by a selected group of hematologists and methodologists with expertise in systematic reviews and guideline development, mainly from United States, without direct connection with pharmaceutical companies. This latter guideline was endorsed by the American Society of Hematology (ASH). A new standardized terminology has also been adopted, with a more clear definition of primary vs secondary ITP and a clear distinction between the different phases of the disease—newly diagnosed, persistent, chronic (after 12 months from diagnosis). Both guidelines structure their suggestions on first, second and third-line treatments, with less attention to the different phases of the disease and its severity. There is a substantial agreement in proposing the initial treatment with oral corticosteroids and TPO-ra as third-line approach in patients unsuccessfully splenectomized in whom these agents appear to have the more favorable therapeutic profile. As to the second-line approach in patients failing corticosteroids, rituximab and TPO-ra could be valid alternatives to splenectomy but, unfortunately, the international guidelines fail to offer a consistent approach. Whereas ICR considers splenectomy at the same level of many other second-line treatments including rituximab and TPO-ra, ASH guideline definitely recommends reserving TPO-ra and rituximab to patients failing or with a contra-indication to splenectomy. As new data are being accumulated on long-term outcomes and toxicity of TPO-ra and the role of rituximab is being better defined for particular patients as second-line therapy, it will be possible to revisit the pros and cons of these options vs each other and splenectomy which, although less and less popular, maintains the highest curative potential, with an acceptable toxicity. The thrombotic risk in ITP should also be better defined and taken into account in guiding the treatment in the individual patients. Hopefully, new studies will be based more on clinical outcomes than on platelet count increase. The ultimate lesson of the insufficient evidence and disagreement among experts is that management of ITP should be tailored to the individual patients.