A rookie mistake. The serif faces Times (in white above) and Garamond (below) are so similar that using them in a sentence won't achieve the needed contrast.

So what should you look for? A principle issue that gets overlooked when pairing fonts is contrast: make sure that they're noticeably different. The key word is noticeably, and some of the following methods will help you pair up different fonts with enough difference to help readers discern one piece of text from another.

Mixing Classes, Qualities

If you were to combine Times and Garamond, the two serif faces are so similar that no differentiation would be evident. However, if you were to combine the serif Times with a Clarendon from the slab serif class, the two are different enough to create a sense of contrast. Moreover, they also have a different weight. Times looks lighter than Clarendon. Other combinations would include pairing a slab serif with a sans serif, script with sans serif, or sans serif with serif.

Slab serifs work well when paired with either serifs or sans serifs.

You can even pair up two narrow fonts, provided that readers will be able to make sense of the hierarchy. The bottom example succeeds where the top one fails because size helps create differentiation.

Consider Weight, Case, and Spacing

If you're not sure about what fonts to pair, just look at the differences in weight. Using a heavier font as a headline or subhead will help create a sense of focus. The text could even be set in a different case, either all caps or small caps, to create further differentiation.

Helvetica Neue and Minion Pro have enough noticeable differences for them to work well together. The topmost setting has both faces set in the same size, and is a less-than-ideal setting. However, the second example from the top has the lowercase x-heights matched up. Lastly, an expanded tracking sets of PREVIEW DAY even more.

Contrasting Styles in One Font

If you are limited to one font and need to create typographic variety, consider how many variants the font has. A face like Myriad Pro includes roman, bold, condensed, and italic styles of each of the preceding three. With Myriad Pro alone, a designer could create enough differentiation to layout an entire book that would include headlines, subheads, body text, captions, and food notes. Myriad Pro is just one of the many fonts that has this breadth. Others, that have been included in software packages such as Adobe's Creative Suite, include Adobe Caslon Pro, Minion Pro, News Gothic, and Helvetica Neue.

Helvetica Neue, available to most users of Adobe Creative Suite, contains a wealth of styles.

Minion Pro also has a lot of styles, with the added bonus of OpenType features such as non-lining (also called Roman) numbers.

With Minion Pro alone, a designer can create enough variation to differentiate multiple content zones.

Make All of the Details Different

In this mock-up, a total of three typefaces have been used: the serif Minion Pro for all the text below the feature photo, Trade Gothic for the title and top-left folio header, and then Copperplate for the year 2011 on the top-right.

Lastly, with the right amount of control, you can set a document in more than two typefaces, provided you spread the differentiation around the document. Whether you follow this principle or any other, keep the golden rule in mind when pairing fonts: make things noticeably different.