There are two safe region types

Safe Countries - Encompasses the Country Chosen
Safe radius regions - Can be any chosen size

When to use Safe Countries?

Use safe country regions when you expect activity to come from various locations within a country such as when a client has both a base of operations and also allows their employees to access Office365 on the move within the same country. On the move will include:

Where employees either work remotely,
Work from home
Or access office 365 on mobile devices on networks outside a fixed office network location.

If any of the above are true then a safe country is applicable.

If none of these are true then you are dealing with a client who is very sensitive about location and/or network access.

When to use Safe Radius Regions?

These act the same as safe countries however are only for specified size and location. There are a few scenarios where they are useful

The client operates in a very large country with many states and cities, many of which you don't expect user activity. Multiple city based radiuses may suffice
The client have a remote worker who is in another country but remains at a fixed or relatively fixed location. A city/region wide radius will suffice
The client is very particular about not allowing access (remote or otherwise) to office 365 outside of their premises network or locality. A single small radius will suffice

Add or update a safe country region

What is a Safe Country Region