Since the first single-cell RNA-sequencing (scRNA-seq) study was published in 2009, many more have been conducted, mostly by specialist laboratories with unique skills in wet-lab single-cell genomics, bioinformatics, and computation. Following the increasing commercial availability of scRNA-seq platforms, and the rapid ongoing maturation of bioinformatics approaches, any biomedical researcher or clinician can use scRNA-seq to make exciting discoveries. Every scRNA-seq protocols require suspensions of viable, single cells as input. The removal of contaminants such as dead cells, debris or unexpected cellular stress reactions from single cell suspensions is critical to obtaining high quality data. Depending on the sample type and sample preparation method, the fraction of these contaminants in a single cell suspension can vary significantly. This can contribute to the background noise of the assay and will compromise the quality of single cell data. In this talk, I will present a practical guide to help researchers design their successful single cell preparation for scRNA-Seq.