Stem cell research has stimulated considerable recent interest, but the concepts are old. Nevertheless, our understanding of the basic biology of different stem cell systems is poor. Many questions remain to be answered: How can we recognize stem cells? Are the underlying control mechanisms common to different types of stem cell, the so-called stemness concept, or is the control of self-renewal and commitment distinct in different stem cell types? What is the significance of differences in stem cells from different species? Do stem cells from somatic tissues really show plasticity with an ability to generate cells from distinct lineages, or are the observed examples consequences of experimental artifact, or rare events of no physiological significance? Do genetic mutations in the genes controlling stem cell self-renewal and differentiation lie at the heart of carcinogenesis? Answers to these and related questions now offer exciting future possibilities for both basic biology and medicine.