The role of A1 and A3 receptors is discussed based on data almost exclusively obtained in the hippocampus. This brain area, where A1 receptor expression predominates, has been a matter of intensive research in the adenosine field. Interestingly, in the last decade, the relevance of the much less expressed adenosine receptor in the hippocampus, the A2A receptor, has been put forward. These two high affinity receptors operate as effective regulators of a number of neurotransmitters and/or neuromodulators, through modulation of their release, action, or even inactivation. Therefore, A1 and A2A receptors constitute a must in the discussion about adenosine receptors in the hippocampus, and consequently, about the potential implications of their pharmacological manipulation and drug targeting.