Linear solvation energy relationships (LSER) have been successfully used to correlate over 300 complex chemical and biochemical properties with small sets of descriptors related to fundamental characteristics of molecular structure and chemistry. This is a branch of the unnamed science (after Hansch) which is concerned with the intricate interactions between chemicals and life. Until recently, the descriptors in these relationships have been empirically determined. Recent developments in both the experimental understanding of these descriptors and in molecular orbital calculations have provided a new ground for fertile interaction between computational and experimental techniques. This manuscript describes development in the use of LSER and the recent molecular orbital formulations which provide basic descriptors developed from fundamental computational techniques. Examples from current research are presented to illustrate the expanding areas of chemistry accessible to these new ideas.