Placenta growth factor (PlGF), a member of the cysteine-knot family, is an angiogenic protein. The PlGF gene has been conserved across different species of the animal kingdom. It is expressed primarily in the placenta, especially in the later stages of gestation. PlGF expression is upregulated during pathological conditions such as ischemia of the heart and myocardial infarction. It is now known that PlGF can modulate the activity of vascular endothelial growth factor, the most potent of all angiogenic inducers and hence makes it an attractive target for therapeutic strategies. Recent structural studies on different isoforms of PlGF promise to reveal important topological and molecular details of these proteins that may be of potential use in the design of effective small molecule inhibitors to combat pathological angiogenesis.