Outlook and emails

Unless a user chooses to "download images" the Marketo tracking pixel will not fire and you will not be able to tell if the email was opened in most clients. 

Gmail is an exception, so people using personal email addresses or on Google Apps for business will have images downloaded automatically unless they opt out. 

It'll never be 100% perfect. This is why I wouldn't really look at opens just in terms of raw numbers. It's more useful in terms of trends and comparing one email to another (i.e., is email A better or wosre than email B in terms of opens, OR, are opens for email A going up or down over time, etc.) rather than being able to say definitively, 4,327 people opened email A. 

What @Justin said, plus realize that if somebody clicks a link, that becomes a "Synthetic Open" even if they never downloaded images, or if they just saw the text-only version of the email.  In other words, you can't use Opens to gauge the useability of images in your emails (both tracking images and marketing-related images) because Marketo logs Opens in other cases as well.