The senior secondary two chemistry course content of the Nigerian science curriculum was assessed using 10 (ten) selected secondary schools in North Central Nigeria, to determine areas of difficulty, magnitude and reasons for such perceived difficulty. Correlation between the students’ perceived difficulty and their achievement in a test and the relationship between the students’ sex and their perceptions of difficulties were also examined using a difficult rating scale questionnaire and a chemistry achievement test. Percentage mean score, mean difficulty indices, person-product-moment correlation and the t-test methods were used for the analysis of the data collected. A total of 10 (ten) out of the 24 (twenty-four) topics identified were perceived as difficult. There was no significant relationship between students’ perceived difficulty and their achievement. Reasons given for the perceived difficulty included unfamiliarity with the ideas, confusing language, ideas too demanding, insufficient explanation and practical work, topics too mathematical and lack of interest among both sexes. Based on these findings, a critical re-assessment of the curriculum was advocated, bearing in mind the cognitive abilities of /and chemistry (science) background of the students. Proper training and re-training (refresher) of teachers was recommended so as to ensure that teaching staff are qualified. Authors of chemistry textbooks should consider the cognitive levels of students of the different levels for choice of suitable vocabulary (language). Teachers should re-examine and evaluate their present teaching strategies so as to be effective and should stop using abstract terms or concepts in the class. Practical work should be emphasized for the acquisition of laboratory skills. The government/proprietors should give priority to equipping the laboratories and improving the teaching and learning environment. Students need counseling, encouragement and enlightenment in order to motivate them in the study of Chemistry. (AJCE, 1(1), January 2011)