Solving the riddle of a thrombocytopenic patient is a difficult and fascinating task. The spectrum of possible aetiologies is wide, ranging from an in vitro artefact to severe treatment-resistant thrombocytopenic bleeding conditions, or even life-threatening prothrombotic states. Moreover, thrombocytopenia by itself does not protect from thrombosis and sometimes a patient with a low platelet count requires concomitant antithrombotic treatment as well. In order to identify and treat the cause and the effects of the thrombocytopenia, you have to put together several pieces of information, solving a unique jig-jaw puzzle. The present work is not a textbook article about thrombocytopenia, rather a collection of differential diagnostic thoughts, treatment concepts, and some basic knowledge, that you can retrieve when facing your next thrombocytopenic patient. Enjoy reading it, but most importantly enjoy taking care of patients with a low platelet count. I bet the present work will assist you in this challenging and rewarding clinical task.