Objective: The aim of this study was to analyze substance abuse and health self-perception in children and adolescents from the province of Cádiz (Spain). Methodology: Participants were 738 students, 50.9 boys and 49.1% girls, from elementary school to high school (1st to 12th grade, mean age 12.2. years), who responded a Spanish adaptation of the Health Behavior in School-aged Children Inventory. Results: No difference was observed in percentage of boys and girls reporting to smoke or drink alcohol. Smoking and drinking habits increased with age, being higher in 11th and 12th grade students. Significant differences were observed among the percentage of smokers and non smokers recognizing to have parents, older brothers or friends who smoke. Rates of drug abuse were generally low, being cannabis the most frequently consumed illicit drug. Most respondents had a perception of excellent or good health, with no significant gender differences. About half of subjects considered that health exclusively depends on self behavior, but an important percentage also gave a relevant role to luck. Stomach-ache was the most frequent physical complaint, followed by headache. Psychological complaints mainly corresponded to nervousness and bad temper. Only a small percentage of subjects declared the use of medicines or tablets without prescription. No significant difference in the percentage of respondent who perceived an excellent or good health was observed among substance users and non users. Conclusions: Substance abuse and health self-perception in children and adolescents are the result of the interaction of a complex series of individual and social factors. Activities aimed to improve health focusing on partial aspects of adolescents' lifestyle most probably will have limited results, and global programs are required.