The p53 tumor suppressor is the guardian of the human genome. Since its discovery in 1979, p53 has been the most studied molecule in the field of cancer. Recently, its role has also been extended to other biological and pathological processes. p53 functions primarily as a transcription factor to regulate target genes that encode proteins crucial for promoting apoptotic cell death, cell cycle arrest, senescence, and so on in response to diverse upstream stressors. Interestingly, some of the p53 targets are noncoding RNAs. Noncoding RNAs can be functional without being translated into proteins and are often independent RNA molecules or noncoding parts of messenger RNAs. The past decade has witnessed burgeoning intensive investigation on the interplay of noncoding RNAs with p53, its regulators, and effectors during the development of cancer and/or other diseases. This issue of Journal of Molecular Cell Biology presents five essays to review the rapid progress in this area from five different angles and to offer new insight into the role of noncoding RNAs in the p53 signaling web with updated information.