Psychological, existential, spiritual, and social issues cause much suffering and deserve extensive study to understand these concerns more fully and to intervene more effectively. Themes that abound include communication, coping, ethics, the family, caregiving, quality of life, death and dying, psychiatric disorders, suffering, and the many expressions of distress. Many study designs are possible to explore these themes, often with complementary quantitative and qualitative components. This chapter summarizes the psychometric properties of many of the instruments that are commonly employed in such studies, and describes quantitative, qualitative, and mixed methods designs used. The goal is to strengthen research design and optimize research outcomes to benefit the discipline.