Accumulating data on non-protein-coding transcripts suggest that besides the regulatory machinery driven by proteins, another yet enigmatic regulatory network of RNA molecules operates and has considerable impact on cell functions. Moreover, deregulation of these non-coding RNAs (ncRNAs) has been documented in several human diseases suggesting that they may significantly contribute to their pathogenesis. This review summarizes our present knowledge on the role of the so-called mRNA-like ncRNAs in the complexity of multicellular organisms. We provide some examples to show how these mRNA-like non-coding RNAs have been discovered, how their cellular functions and role in the pathogenesis of human diseases have been revealed.