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Poor knowledge could be a precursor to substance abuse among adolescents. Prior to program development, it is necessary to know about the knowledge, attitude and perceptions about drug abuse in this population. The objective of this study was to explore the knowledge, attitude, perceived consequences of substance abuse among secondary school students in Jizan city, Kingdom of Saudi Arabia. This descriptive study included a representative sample of male secondary school students. A multistage random sample was generated. A self administered validated and reliable Arabic questionnaire was used. Knowledge scores were computed such that correct answer was given a score of 1 while incorrect and unknown answers were given a score of zero. The percentage of correct answers was computed for the sample. Mean percentage of knowledge score >60% was considered sufficient knowledge while 60% was considered insufficient knowledge. Out of 1100 male secondary students invited to participate in the study, 1022 returned filled questionnaire giving a response rate of 92.9%. Their age ranged between 15 and 19 years with a mean of 17.33 and standard deviation of 0.98 years. The great majority of them (99.7%) have heard about substance abuse and 83.8% claimed that they have information about different abused substances. Their sources of information about substance abuse were internet (71.1%), TV/Radio (61%), friends (55.5%), schools (43.9%), family members (33.8%) and finally newspapers and magazines (31.2%).Most of male students in Jizan had sufficient knowledge regarding substance abuse.