The development of genome-wide gene expression profiling technologies over the past two decades has produced great opportunity for researchers to explore the transcriptome and to better understand biological systems and their perturbation. In this chapter we provide an overview of microarray and massively parallel sequencing technologies and their application to gene expression analysis. We discuss factors that impact expression data generation and analysis that which should be considered in the application of these technology platforms. We further present the results of a simple illustration study to highlight performance similarities and differences in expression profiling of protein-coding mRNAs with each platform. Based on technical and analytical differences between the two platforms, reports in the literature comparing arrays and RNA-Seq for gene expression, and our own example study and experience, we provide recommendations for platform selection for gene expression studies.