High performance liquid chromatography (HPLC) has developed into a useful tool for chemical analysis. While there is a considerable number of HPLC studies in the scientific literature, a need exists for further development of existing methodologies and for novel devel- opments. Essentially, the capability of specific analyses that provide appropriate data, with statistical confidence, will limit the type and, thus, the complexity of the chemical system under investigation. In the specific context of using HPLC, developments in three distinct areas are presented and discussed in detail;It has been accepted that qualitative analysis must precede quantitative analysis in applying any analytical procedure. This severely limits the scope of chemical systems that may be studied, unless appropriate chemical standards are available. Investigations have shown that quantitative analysis may be performed concurrent with qualitative analysis, thus, solving this problem. These results are presented for HPLC systems using a refractive index detector;In HPLC, the limit of detection, as conventionally defined, becomes worse with increased retention due to band broadening. An integration method is presented and studied that overcomes this limitation, to a large extent, providing better analyte detectabilities;The advent of microbore HPLC technology has brought about the need for developing small volume detectors without sacrificing detectability or selectivity. Application of lasers, as the light source, has helped to solve this problem for a variety of spectroscopic and optical detection principles. Both transmission detected circular;dichroism and fluorescence detected circular dichroism were studied and developed into laser-based HPLC detection systems; *This work was performed under contract W-7405-eng-82 with the U.S. Department of Energy.