In the summer of 2008, Principles of Biochemistry was redesigned as a fully online, vodcasted course. The journey to design such a course involved much formative evalu- ation and relied heavily on earlier data from podcasting and vodcasting trials in General Microbiology. While formative data were highly positive, they did show that vodcasts still sometimes lacked personal interaction. Thus in creating the vodcasts for Biochemistry, great attention is paid to nurturing feelings of connectedness. Towards these ends, vod- casts are often delivered in an informal way with demonstrations and students are even “invited into my home” as we talk about vitamin cofactors, the principles of metabolism as they relate to wine-making and carbohydrate macromolecular structure. Examples, jokes and demonstrations are used to help students connect to the content. Many exam- ples relating to students’ lives are included as is positive feedback, praise and incentive. The vodcasts encourage students to keep working on their “sexy minds.” Vodcasts are also used as a forum for role modeling. This contrasts greatly with traditional computer-based instruction. Office hours for this course are held on both Elluminate (Blackboard Collaborate) and Second Life. Office hours in Second Life enable “field trips” to Islands such as Genome Island on which avatars can interact with models of cells, proteins and even stroll in a garden of prokaryotic plasmids.