Long non-coding RNAs (lncRNAs) are defined as a class of nonprotein-coding transcripts greater than 200 nucleotides in length, which have diverse functions in development and diseases including hematopoiesis. Recent advances have revealed that lncRNAs regulate hematopoietic development at almost every stage, including differentiation of the myelocyte, lymphocyte, and erythrocyte. Abnormal regulation of the lncRNAs may block aspects of blood development, which can lead to different types of hematopoietic disorders. These findings highlight the role of lncRNAs as potential therapeutic tools in malignant hematopoiesis. In this review, we summarize recent progress in the study of functional lncRNAs associated with blood development, as well as dysregulated lncRNAs involved in diverse blood diseases by interacting with crucial susceptibility genes in different pathways. In addition, we discuss genome-wide studies on lncRNAs, which are helpful for genome screening and in-depth functional study of lncRNAs associated with blood development and disease.