This question originally appeared on Quora. 
Answer by Stephen Coles, Editor, Typographer, stephencoles.org, and typeanatomy.com
The quickest way for a novice to distinguish these typefaces is by the terminals (ends) on curved strokes. Are they mostly angled, vertical, or horizontal? Of course, this is dramatically simplifying things and there are lots of other differences, but this is the most apparent distinguisher, visible across most of the lowercase of each typeface.
Helvetica (classified as a "Grotesque", "Neo-Grotesque", "Static", or "Rational" sans serif) is more distinct from the other two because it is has a much more "machined" appearance, with horizontal terminals, closed apertures, and very normalized lettershapes and widths. In addition, Helvetica's round shapes are more square than Myriad and Frutiger, its x-height is larger, and its ascenders are shorter.
As typefaces in the "Humanist" category, Frutiger and Myriad have much more in common with each other than with Helvetica. Their lettershapes are more closely related to the gentle curves of handwriting. Frutiger has a slightly crisper feel, partly because its terminals are sheared nearly vertically, whereas Myriad's terminals end perpendicular to the stroke direction.
More questions on Typefaces: