For patients with antiphospholipid syndrome (APS), the consensus is to treat those who develop thrombosis with long-term oral anticoagulation therapy and to prevent obstetric manifestations by use of aspirin and heparin. These recommendations are based on data from randomized controlled trials and observational studies. Despite this body of knowledge, areas of uncertainty regarding the management of APS exist where evidence is scarce or nonexistent. In other words, for a subset of patients the course of management is unclear. Some examples are patients with 'seronegative' APS, those who do not fulfil the formal (clinical or serological) classification criteria for definite APS, and those with recurrent thrombotic events despite optimal anticoagulation. Other challenges include the treatment of clinical manifestations not included in the classification criteria, such as haematologic manifestations (thrombocytopenia and haemolytic anaemia), neurologic manifestations (chorea, myelitis and multiple sclerosis-like lesions), and nephropathy and heart valve disease associated with antiphospholipid antibodies (aPL), as well as the possible withdrawal of anticoagulation treatment in selected cases of thrombotic APS in which assays for aPL become persistently negative. This Review focuses on the current recommendations for thrombotic and obstetric manifestations of APS, as well as the management of difficult cases. Some aspects of treatment, such as secondary prophylaxis of venous thrombosis, are based on strong evidence--the 'lights' of APS treatment. Conversely, other areas, such as the treatment of non-criteria manifestations of APS, are based only on expert consensus or common sense and remain the 'shadows' of APS therapy.