Despite the long history of research that has focused on the role of defects on device performance, the studies have not always been fruitful. A major reason is because these defect studies have typically been conducted in a parallel mode wherein the semiconductor wafer was divided into multiple pieces for separate optical and structural characterization, as well as device fabrication and evaluation. The major limitation of this approach was that either the defect being investigated by structural characterization techniques was not the same defect that was affecting the device performance or else the defect was not characterized under normal device operating conditions. In this review, we describe a more comprehensive approach to defect study, namely a series mode, using an array of spatially-resolved optical, electrical, and structural characterization techniques, all at the individual defect level but applied sequentially on a fabricated device. This novel sequential approach enables definitive answers to key questions, such as: (i) how do individual defects affect device performance? (ii) how does the impact depend on the device operation conditions? (iii) how does the impact vary from one defect to another? Implementation of this different approach is illustrated by the study of individual threading dislocation defects in GaAs solar cells. Additionally, we briefly describe a 3-D Raman thermometry method that can also be used for investigating the roles of defects in high power devices and device failure mechanisms.