Studies show that students perform poorly at the secondary school level in biology. The concepts considered as difficult contribute more to the poor performance. The fact remains that the topics related to these concepts are found to be difficult by the teachers teaching them. The undesirable trend has been attributed among other reasons to ineffective pedagogy among teachers of biology. This problem led to an upsurge of research into innovative approaches that can alleviate the situation. One such emerging approach advocated here is the use of 5Es' constructivist approach. The approach advocates problem solving learning atmosphere where learners are effectively guided to take responsibility for their learning, the effective utilization of which can enhance biology teaching and learning. This paper focused on how this approach could be applied in teaching one of the identified difficult concepts in biology namely; respiration. Some empirical studies on the effectiveness of the constructivist-based methods when compared with other approaches were reviewed. A sample of note of lesson using the 5Es' approach and guide was designed. It was recommended among others that government as well as professional associations should organize training for biology teachers on the use of 5Es' learning cycle as effective teaching approach.