We have briefly discussed herein four of the many aspects that raise concerns in the context of implementation of whole-exome and whole-genome sequencing (mainly) in the clinical realm. Namely, we addressed issues surrounding: (1) the duty to hunt for variants known to have a health impact, (2) such “hunting” or opportunistic screening in children, (3) challenges to the consent process, and (4) the commercialization of genetic testing direct to consumer.