This review summarizes the current tendencies observed in the past 5 years in the development of A1 and A2A adenosine receptor antagonists performed in various academia and industry. A1 and A2A AR antagonists are as well xanthines as heteroaromatic derivatives and are most commonly 6:5 fused heteroatomic compounds. Among xanthine-based compounds, some common features could be pointed out. The recent A1 AR ligands which show good biological profile, possess long alkyl chains in position 1 and 3 as well as bulky C(8)- substituent, while A2A AR antagonists with a high A2A AR affinity are C(8)-styryl substituted with N(1)- alkyl/alkynyl moiety or fused tricyclic xanthines possessing heteroatom(s) in the third cycle. The research in the field of heteroaromatic A1 and A2A ARs antagonists impressively has a wide range. Ligands are as well non-fused monocyclic substituted compounds as fused bi- and tricyclic derivatives with the nitrogen, oxygen and sulfur heteroatoms. Most often, adenosine A1 receptor non-xanthine antagonists are adenine-based, having substituted amino group and variable nitrogen atoms positions in the molecules. A2A AR ligands show good affinity when furanyl function, which is crucial for binding, is present in the fused bicyclic and tricyclic analogs. Moreover, tricyclic nitrogen containing antagonists in order to be active, frequently possess long-alkylphenyl moiety.