Microfluidic devices on chip-based systems are becoming increasingly popular, because of many advantages, like low mobile phase consumption and greatly reduced analysis times. The ultimate goal is to design all-including labon- a-chip tools that can be employed in the field and that integrate all elements necessary for an analysis, e.g. one or more separation channels, (multiple) detectors, mixing chambers and sample pretreatment areas. The chip format permits to make any channel pattern, rendering the applications of lab-on-a-chip unlimited. However, overcoming the limitations inherent with the detection systems remains a challenging problem. Whereas UV-detection is predominant in the larger systems, its sensitivity is inadequate due to the minute pathlengths employed in a chip. This review summarizes the shortcomings of UV detection, and discusses some possible solutions. Besides, it presents an overview of the alternative detection methods that have been employed in pharmaceutical and chiral chip analysis, including their positive and negative aspects as well. Finally, the applications reported on the chips are discussed.