The structure-activity relationships of chemically modified analogs of neurohypophyseal hormons oxitocin, OT, and vasopressin, VP, possessing both agonistic and antagonistic activities are considered on several levels of the insight into details of chemical structure and interaction. First, some of our early attempts to develop analogues of OT and VP with modified biological properties, by applying one-by-one amino acid residue replacements to the mother hormone sequence, are described. Susequently, our recent efforts with the use of QSAR (Quantitative Structure Activity Relationships) analysis for the vast selection of analogs of OT and VP are recapitulated. In the last part of the article some of our current results related to spatially constrained OT antagonists, aimed at the definition of an OT antagonist pharmacophore are presented.