Radiotherapy　(RT)　based　on　X-ray　irradiation　is　a　widely　applied　cancer　treatment　strategy　in　the　clinic.　However,　treating　cancer　based　on　RT　alone　usually　results　in　insufficient　radiation　energy　deposition,　which　inevitably　has　serious　side　effects　on　healthy　parts　of　the　body.　Interestingly,　high　atomic　number　(high-Z)　metal　nanocrystals　as　X-ray　sensitizers　can　reduce　the　radiation　dose　effectively　due　to　their　high　X-ray　absorption,　which　has　attracted　increased　attention　in　recent　years.　High-Z　metal　nanocrystals　produce　Auger　and　photoelectrons　electrons　under　X-ray　irradiation,　which　could　generate　large　amounts　of　reactive　oxygen　species,　and　induce　cellular　damages.　The　sensitization　effect　of　high-Z　metal　nanocrystals　is　closely　related　with　their　composition,　morphologies,　and　size,　which　would　strongly　impact　their　performances　in　the　application　of　cancer　imaging　and　therapy.　In　this　review,　we　summarize　diverse　types　of　X-ray　sensitizers　such　as　bismuth,　hafnium,　gold,　and　gadolinium　for　cancer　RT　and　imaging　applications.　In　addition,　current　challenges　and　the　outlook　of　RT　based　on　high-Z　metal　nanocrystals　are　also　discussed.　[Figure　not　available:　see　fulltext.]　©　2021,　Tsinghua　University　Press　and　Springer-Verlag　GmbH　Germany,　part　of　Springer　Nature.