Neanderthals represent an extinct hominid lineage that existed in Europe and Asia for nearly 400,000 years. They thrived in these regions for much of this time, but declined in numbers and went extinct around 30,000 years ago. Interestingly, their disappearance occurred subsequent to the arrival of modern humans into these areas, which has prompted some to argue that Neanderthals were displaced by better suited and more adaptable modern humans. Still others have postulated that Neanderthals were assimilated into the gene pool of modern humans by admixture. Until relatively recently, conclusions about the relationships between Neanderthals and contemporary humans were based solely upon evidence left behind in the fossil and archaeological records. However, in the last decade, we have witnessed the introduction of metagenomic analyses, which have provided novel tools with which to study the levels of genetic interactions between this fascinating Homo lineage and modern humans. Were Neanderthals replaced by contemporary humans through dramatic extinction resulting from competition and/or hostility or through admixture? Were Neanderthals and modern humans two independent, genetically unique species or were they a single species, capable of producing fertile offspring? Here, we review the current anthropological, archaeological and genetic data, which shed some light on these questions and provide insight into the exact nature of the relationships between these two groups of humans.