Many mainstream content teachers are encountering, for the first time, K-12 students who are in the process of learning English as a second language (English language learners or ELLs), and this new population presents a significant challenge. Teachers are already familiar with many of the techniques available to help their ELLs comprehend instruction given in English. By combining these techniques in an approach that uses multiple modes of input and output (MMIO), teachers can make content comprehensible and assessment possible for their ELLs. This article presents: (1) three steps for using MMIO; (2) using MMIO for Comprehensible Input in a Cell Inquiry Lesson; and (3) using MMIO for Comprehensible Output in a Cell Inquiry Lesson. It is concluded that using the MMIO approach to present key concepts in multiple ways that are less language dependent enables teachers to make instruction more accessible for their ELLs, better assess student progress, and promotes English language development.