Connection files allow EndNote to communicate with another database, allowing you to search a resource like PubMed from within EndNote.
Advantages
1. If you are missing a known reference from your library, you can quickly add the citation and a pdf to your library.
2. If you have a very unique term or author name you are following, it may be easy to have EndNote pull relevant citations to your library.
Disadvantage
This is the big one: PubMed uses something called automatic term mapping. When you type a word or phrase like heart attack into the PubMed search box, PubMed automatically searches synonymous terms like myocardial infarction at the same time. EndNote does not do this. So if you enter the phrase "heart attack" that is all you'll get and your search results may suffer. If you are conducting a literature review then its usually best to stick to the native search functions within the database you wish to search.
EndNote comes with most of the connection files you need. To learn about connection files and how to use them, watch this helpful video.