Gene therapy has only recently begun to make serious progress, beginning with two approved gene therapy trials in the United States In late 1990. The death of an 18-year-old man participating in a gene therapy trial delivered a major setback in terms of public concerns, but the resulting improvements in scrutiny of trial design and ethical standards will benefit the field in the long run. The three main issues for the coming decade will be public perceptions, scale-up and manufacturing, and commercial considerations. Focusing on single-gene applications, which tend to be rarer diseases, will produce successful results sooner than the current focus on the commoner, yet more complex, cancer and heart disease.