Antiphospholipid (APL) syndrome is the most common form of acquired thrombophilia. It can cause significant morbidity and even mortality. The term “APL antibodies” represents a heterogeneous group of antibodies associated with this disorder. Currently no single assay can identify every APL antibody. Clinically relevant APL antibodies are mainly anticardiolipin antibodies (ACA) detected by solid phase enzyme-linked immunosorbent assay (ELISA) and lupus anticoagulants (LA) demonstrated by in vitro coagulation assay. However, there are some other antibodies associated with the APL syndrome (i.e., subgroup APL antibodies). ACAs, LAs, and subgroup APL antibodies represent intersecting, but non-identical, subsets of autoantibodies. Thus, those autoantibodies may coexist or may occur independently. Any organ system and any size of vessel can be affected during the clinical course of the disease. Therefore, the APL syndrome can manifest itself in a wide variety of clinical thrombotic features. Fetal loss and pregnancy morbidity represent a specific challenge. Despite tremendous advances in the understanding of the pathogenesis of APL syndrome during the past decade, the mainstay of management is still anticoagulation. However, there is no general agreement regarding the duration and intensity of anticoagulant therapy. In this review, we focused on the current dilemmas and their present clarifications in the wide clinicopathologic spectrum of APL syndrome and APL antibody-related distinct pathologic conditions.