Noncoding small RNAs arise from the various un-annotated and annotated regions of the genome. When they arise from annotated genes, the noncoding small RNAs are functionally different from the parent genes. This is a brief review of one class of noncoding small RNAs, tRNA-related fragments (tRFs), which are generated from tRNA. tRFs have been suggested to have roles in cell proliferation, priming of viral reverse transcriptases, regulation of gene expression, RNA processing, modulation of the DNA damage response, tumor suppression, and neurodegeneration.